Kava Kava (KAV) is a plant-derived treatment which is widely used in Europe to treat anxiety states. Three double-blind trial in anxiety disorders have shown greater efficacy for KAV than placebo (PBO), and two have reported efficacy equal to benzodiazepines. However, a number of problems exist in respect to the design of these trials, which restricts their generalizability. Nonetheless, evidence from both basic science and clinical studies support the likelihood of an anxiolytic effect of kava. With public interest in phytotherapy for depression and anxiety now on the rise in the US, we propose to evaluate KAV in generalized anxiety disorder (GAD), relative both to PBO and an active drug, venelafaxine-XR, known to be effective in GAD. We will enroll 124 patients into the study to obtain 93 completers (n = 31 KAV, n = 31 PBO, n = 31 VEN). After 8 weeks of treatment, subjects will undergo a one-week taper, followed by an additional week's observation. Doses of up to 280 mg/day standardized active kavalactone extract and 225 mg/day VEN, or matching PBO, will be used. The primary efficacy measure will be the HAM-A. Secondary measures will comprise the Clinical Global Impressions Improvement Scale (CGI-I), Hospital Anxiety and Depression Scale (HADS), Penn State Worry Inventory (PSWI), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions Severity Scale (CGI-S), Short Form-36 (SF-36), Work and Social Disability Scale (WSDS), Sheehan Disability Scale (SDS), and Work Productivity and Impairment Questionnaire (WPAI). Side-effects, vital signs, and laboratory measures will be monitored. Treatment will be monitored for treatment integrity and an independent rater will be used for key outcome assessments. The potential benefit of this study might be the identification of an effective herbal medical treatment for GAD which is safe and well tolerated. It will also contribute towards providing an answer to what is rapidly becoming a major public health question, namely what can we reasonably expect herbal treatments to offer?